title: CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter TIP5.
abstract: Despite the well-established fact that NuRD (nucleosome remodeling and histone deacetylase) is incapable of actively demethylating DNA, the complex is surprisingly showed to be required for the establishment of unmethylated state at promoters of ribosomal genes. But the molecular mechanism underlying how NuRD mediates unmethylation at rDNA promoters remains obscure. Here we show that NuRD directly binds to the promoter of rDNA transcription silencer TIP5 (TTF-I interacting protein 5), one of the components of nucleolar remodeling complex NoRC that silences rRNA genes by recruiting DNA methyltransferase to rDNA promoters and increasing DNA methylation. NuRD negatively regulates TIP5 expression, thereby inhibiting rDNA methylation and maintaining demethylation state of rDNA promoters. The deficiency of NuRD components in reprogrammed cells activates TIP5 expression, resulting in the increased fraction of heterochromatic rRNA genes and transcriptional silencing. Thus, NuRD is able to control methylation status of rDNA promoters through crosstalking with NoRC complex.
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors.forename: Te
authors.initials: T
authors.lastname: Ling
authors.forename: Wenbing
authors.initials: W
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Meili
authors.initials: M
authors.lastname: Shen
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Zhu
authors.forename: Le
authors.initials: L
authors.lastname: Zong
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Feixiong
authors.initials: F
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D020459:Genes, rRNA; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D004275:DNA, Ribosomal; D008780:Methyltransferases; D012097:Repressor Proteins; C499051:Baz2a protein, mouse; D000092468:Bromodomain Containing Proteins; C509277:Mi-2beta protein, mouse
keywords: DNA methylation; NoRC; Reprogramming; TIP5; rRNA genes